The prime objective of our research is to determine whether specific molecular alterations or lesions exist in the nuclear envelopes of tumor cells. Such changes which could perturb nuclear function in terms of nucleocytoplasmic transport, responsiveness to various intra-and/or extranuclear effectors, and specific enzymic pathways may in part account for changes in replication behavior as well as other properties associated with the neoplastic state. The studies involve the chemical and biochemical characterization of nuclear envelopes (composed of both inner and outer leaflets) from normal and neoplastic cells at the level of intrinsic membrane proteins and their subunits (structure, composition, and physical properties), biosynthesis and degradation, antigenic similarities and differences, and biochemical behavior. In view of the fact that the outer nuclear leaflet forms a morphological continuum with the endoplasmic reticulum, a parallel structural and functional analysis of the microsomal membrane is also undertaken in an attempt to more fully define membrane associated changes related to transformation.